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Background Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. Methods Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. Results Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. Conclusions The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions. [ABSTRACT FROM AUTHOR]

Globally, there are over 1 billion people infected with soil-transmitted helminths (STHs), mostly living in marginalized settings with inadequate sanitation in sub-Saharan Africa and Southeast Asia. The World Health Organization recommends an integrated approach to STH morbidity control through improved access to sanitation and hygiene education and the delivery of preventive chemotherapy (PC) to school-age children delivered through schools. Progress of STH control programs is currently estimated using a baseline (pre-PC) school-based prevalence survey and then monitored using periodical school-based prevalence surveys, known as Impact Assessment Surveys (IAS). We investigated whether integrating geostatistical methods with a Markov model or a mechanistic transmission model for projecting prevalence forward in time from baseline can improve IAS design strategies. To do this, we applied these 2 methods to prevalence data collected in Kenya, before evaluating and comparing their performance in accurately informing optimal survey design for a range of IAS sampling designs. We found that, although both approaches performed well, the mechanistic method more accurately projected prevalence over time and provided more accurate information for guiding survey design. Both methods performed less well in areas with persistent STH hotspots where prevalence did not decrease despite multiple rounds of PC. Our findings show that these methods can be useful tools for more efficient and accurate targeting of PC. The general framework built in this paper can also be used for projecting prevalence and informing survey design for other neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a multifaceted global health problem disproportionately affecting low- and middle-income countries (LMICs). The Capturing data on Antimicrobial resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) project was tasked to expand the volume of AMR and antimicrobial use data in Asia. The CAPTURA project used 2 data-collection streams: facility data and project metadata. Project metadata constituted information collected to map out data sources and assess data quality, while facility data referred to the retrospective data collected from healthcare facilities. A down-selection process, labelled "the funnel approach" by the project, was adopted to use the project metadata in prioritizing and selecting laboratories for retrospective AMR data collection. Moreover, the metadata served as a guide for understanding the AMR data once they were collected. The findings from CAPTURA's metadata add to the current discourse on the limitation of AMR data in LMICs. There is generally a low volume of AMR data generated as there is a lack of microbiology laboratories with sufficient antimicrobial susceptibility testing capacity. Many laboratories in Asia are still capturing data on paper, resulting in scattered or unused data not readily accessible or shareable for analyses. There is also a lack of clinical and epidemiological data captured, impeding interpretation and in-depth understanding of the AMR data. CAPTURA's experience in Asia suggests that there is a wide spectrum of capacity and capability of microbiology laboratories within a country and region. As local AMR surveillance is a crucial instrument to inform context-specific measures to combat AMR, it is important to understand and assess current capacity-building needs while implementing activities to enhance surveillance systems. [ABSTRACT FROM AUTHOR]

Background There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. Methods We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014–2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. Results Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval,.39–.68] and.40 [.27–.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02–4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. Conclusions Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) use between October and December 2020 was characterized using the National Inpatient Sample database. CCP was administered in 18.0% of COVID-19-associated hospitalizations and was strongly associated with older age and increased disease severity. There were disparities in the receipt of CCP by race and ethnicity, geography, and insurance. [ABSTRACT FROM AUTHOR]

Background Tuberculosis case-finding interventions are critical to meeting World Health Organization End TB strategy goals. We investigated the impact of community-wide tuberculosis active case finding (ACF) alongside scale-up of human immunodeficiency virus (HIV) testing and care on trends in adult tuberculosis case notification rates (CNRs) in Blantyre, Malawi. Methods Five rounds of ACF for tuberculosis (1–2 weeks of leafleting, door-to-door enquiry for cough and sputum microscopy) were delivered to neighborhoods ("ACF areas") in North-West Blantyre between April 2011 and August 2014. Many of these neighborhoods also had concurrent HIV testing interventions. The remaining neighborhoods in Blantyre City ("non-ACF areas") provided a non-randomized comparator. We analyzed TB CNRs from January 2009 until December 2018. We used interrupted time series analysis to compare tuberculosis CNRs before ACF and after ACF, and between ACF and non-ACF areas. Results Tuberculosis CNRs increased in Blantyre concurrently with start of ACF for tuberculosis in both ACF and non-ACF areas, with a larger magnitude in ACF areas. Compared to a counterfactual where pre-ACF CNR trends continued during ACF period, we estimated there were an additional 101 (95% confidence interval [CI] 42 to 160) microbiologically confirmed (Bac+) tuberculosis diagnoses per 100 000 person-years in the ACF areas in 3 and a half years of ACF. Compared to a counterfactual where trends in ACF area were the same as trends in non-ACF areas, we estimated an additional 63 (95% CI 38 to 90) Bac + diagnoses per 100 000 person-years in the same period. Conclusions Tuberculosis ACF was associated with a rapid increase in people diagnosed with tuberculosis in Blantyre. [ABSTRACT FROM AUTHOR]

Background Malaria during pregnancy can cause serious consequences including maternal anemia and low birthweight (LBW). Routine antenatal care (ANC) in Rwanda includes malaria symptom screening at each ANC visit. This cluster randomized controlled trial investigated whether adding intermittent screening with a malaria rapid diagnostic test at each routine ANC visit and treatment of positives during pregnancy (ISTp) is more effective than routine ANC for reducing malaria prevalence at delivery. Methods Between September 2016 and June 2018, pregnant women initiating ANC at 14 health centers in Rwanda were enrolled into ISTp or control arms. All women received an insecticide-treated bed net at enrollment. Hemoglobin concentration, placental and peripheral parasitemia, newborn outcome, birthweight, and prematurity were assessed at delivery. Results Nine hundred seventy-five women were enrolled in ISTp and 811 in the control group. Routine ANC plus ISTp did not significantly reduce polymerase chain reaction–confirmed placental malaria compared to control (adjusted relative risk [aRR], 0.94 [95% confidence interval {CI},.59–1.50]; P =.799). ISTp had no impact on anemia (aRR, 1.08 [95% CI,.57–2.04]; P =.821). The mean birthweight of singleton newborns was not significantly different between arms (3054 g vs 3096 g, P =.395); however, women in the ISTp arm had a higher proportion of LBW (aRR, 1.59 [95% CI, 1.02–2.49]; P =.042). Conclusions This is the only study to compare ISTp to symptomatic screening at ANC in a setting where intermittent preventive treatment is not routinely provided. ISTp did not reduce the prevalence of malaria or anemia at delivery and was associated with an increased risk of LBW. Clinical Trials Registration NCT03508349. [ABSTRACT FROM AUTHOR]

Background Since 2014, multiple outbreaks of human immunodeficiency virus (HIV) among people who inject drugs have occurred across the United States along with hepatitis C virus (HCV), skin and soft tissue infections (SSTIs), and infective endocarditis (IE), creating a converging public health crisis. Methods We analyzed the temporal patterns of infectious disease and overdose using a hierarchical Bayesian distributed lag logistic regression model examining the probability that a given geographic area experienced at least 1 HIV case in a given month as a function of the counts/rates of overdose, HCV, SSTI, and IE and associated medical procedures at different lagged time periods. Results Current-month HIV is associated with increasing HCV cases, abscess incision and drainage, and SSTI cases, in distinct temporal patterns. For example, 1 additional HCV case occurring 5 and 7 months previously is associated with a 4% increase in the odds of observing at least 1 current-month HIV case in a given locale (odds ratios, 1.04 [90% credible interval {CrI}: 1.01–1.10] and 1.04 [90% CrI: 1.00–1.09]). No such associations were observed for echocardiograms, IE, or overdose. Conclusions Lagged associations in other infections preceding rises in current-month HIV counts cannot be described as predictive of HIV outbreaks but may point toward newly discovered epidemics of injection drug use and associated clinical sequalae, prompting clinicians to screen patients more carefully for substance use disorder and associated infections. [ABSTRACT FROM AUTHOR]

Background The human immunodeficiency virus (HIV) type 1 A6 variant is dominating in high-prevalence Eastern European countries, with increasing prevalence over the remaining regions of Europe. The recent war in Ukraine may contribute to further introductions of this A6 lineage. Our aim was to model the transmission dynamics of the HIV-1 A6 variant between Poland and Ukraine. Methods HIV-1 A6 partial pol sequences originating from Poland (n = 1185) and Ukraine (n = 653) were combined with publicly available sequences (n = 7675) from 37 other countries. We used maximum likelihood-based tree estimation followed by a bayesian inference strategy to characterize the putative transmission clades. Asymmetric discrete phylogeographic analysis was used to identify the best-supported virus migration events across administrative regions of Poland and Ukraine. Results We identified 206 clades (n = 1362 sequences) circulating in Poland or Ukraine (63 binational clades, 79 exclusively Polish, and 64 exclusively Ukrainian). Cross-border migrations were almost exclusively unidirectional (from Ukraine to Poland, 99.4%), mainly from Eastern and Southern Ukraine (Donetsk, 49.7%; Odesa, 17.6% regions) to the Central (Masovian, 67.3%; Lodz, 18.2%) and West Pomeranian (10.1%) districts of Poland. The primary sources of viral dispersal were the Eastern regions of Ukraine, long affected by armed conflict, and large population centers in Poland. Conclusions The Polish outbreak of the A6 epidemic was fueled by complex viral migration patterns across the country, together with cross-border transmissions from Ukraine. There is an urgent need to include war-displaced people in the national HIV prevention and treatment programs to reduce the further spread of transmission networks. [ABSTRACT FROM AUTHOR]

Background Limited information exists about testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among Medicaid enrollees after starting medication for opioid use disorder (MOUD), despite guidelines recommending such testing. Our objectives were to estimate testing prevalence and trends for HIV, HBV, and HCV among Medicaid enrollees initiating MOUD and examine enrollee characteristics associated with testing. Methods We conducted a serial cross-sectional study of 505 440 initiations of MOUD from 2016 to 2019 among 361 537 Medicaid enrollees in 11 states. Measures of MOUD initiation; HIV, HBV, and HCV testing; comorbidities; and demographics were based on enrollment and claims data. Each state used Poisson regression to estimate associations between enrollee characteristics and testing prevalence within 90 days of MOUD initiation. We pooled state-level estimates to generate global estimates using random effects meta-analyses. Results From 2016 to 2019, testing increased from 20% to 25% for HIV, from 22% to 25% for HBV, from 24% to 27% for HCV, and from 15% to 19% for all 3 conditions. Adjusted rates of testing for all 3 conditions were lower among enrollees who were male (vs nonpregnant females), living in a rural area (vs urban area), and initiating methadone or naltrexone (vs buprenorphine). Associations between enrollee characteristics and testing varied across states. Conclusions Among Medicaid enrollees in 11 US states who initiated medications for opioid use disorder, testing for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and all 3 conditions increased between 2016 and 2019 but the majority were not tested. [ABSTRACT FROM AUTHOR]

Background: Despite antibiotic prescription being recommended for dysentery and suspected cholera only, diarrhea still triggers unwarranted antibiotic prescription. We evaluated antibiotic-prescribing practices and their predictors among children aged 2–59 months in the Vaccine Impact on Diarrhea in Africa (VIDA) Study performed in The Gambia, Mali, and Kenya. Methods: VIDA was a prospective case-control study (May 2015–July 2018) among children presenting for care with moderate-to-severe diarrhea (MSD). We defined inappropriate antibiotic use as prescription or use of antibiotics when not indicated by World Health Organization (WHO) guidelines. We used logistic regression to assess factors associated with antibiotic prescription for MSD cases who had no indication for an antibiotic, at each site. Results: VIDA enrolled 4840 cases. Among 1757 (36.3%) who had no apparent indication for antibiotic treatment, 1358 (77.3%) were prescribed antibiotics. In The Gambia, children who presented with a cough (adjusted odds ratio [aOR]: 2.05; 95% confidence interval [95% CI]: 1.21–3.48) were more likely to be prescribed an antibiotic. In Mali, those who presented with dry mouth (aOR: 3.16; 95% CI: 1.02–9.73) were more likely to be prescribed antibiotics. In Kenya, those who presented with a cough (aOR: 2.18; 95% CI: 1.01–4.70), decreased skin turgor (aOR: 2.06; 95% CI: 1.02–4.16), and were very thirsty (aOR: 4.15; 95% CI: 1.78–9.68) were more likely to be prescribed antibiotics. Conclusions: Antibiotic prescription was associated with signs and symptoms inconsistent with WHO guidelines, suggesting the need for antibiotic stewardship and clinician awareness of diarrhea case-management recommendations in these settings. Inappropriate antibiotic prescribing for diarrheal diseases can promote antimicrobial resistance. In VIDA, unnecessary or incorrect antibiotics were prescribed for 77% of diarrhea and 41% of dysentery cases. Interventions are needed to promote judicious adherence to international guidelines in low-/middle-income countries. [ABSTRACT FROM AUTHOR]

The authors comment on a study published within the issue which aimed to identify the proportion of infectious disease (ID) physicians who possessed a buprenorphine waiver. Topics covered include individual- and country-level characteristics associated with the possession of buprenorphine possession, the strengths and limitations of the study, and factors that contribute to ID physicians' decision to provide opioid use disorder (OUD) care,

Background Persons with opioid use disorder (OUD) may present with infectious complications from injection drug use; thus, infectious diseases (ID) physicians are uniquely positioned to treat OUD. Buprenorphine is safe and effective for OUD but remains underutilized. The prevalence and geographic distribution of ID physicians who are waivered to prescribe buprenorphine are unknown. Methods This cross-sectional study merged data from several publicly available datasets from 1 November 2021 to 15 January 2022. Our primary outcome was the proportion of ID physicians possessing buprenorphine waivers in the United States. We identified individual- and county-level characteristics associated with buprenorphine waiver possession. We then used geospatial analysis to determine the geographic distribution of waivered ID physicians. Results We identified 6372 ID physicians in the United States, among whom 170 (2.7%) possessed waivers. Most ID physicians (97.3%) practiced in metropolitan counties. In our multivariable analysis, ID physicians had lower odds of having a waiver for every 10-year increase since graduating medical school (OR:.79; 95% CI:.68–.91). ID physicians practicing in counties with a higher proportion of uninsured residents had lower odds of having a waiver (OR:.75; 95% CI:.62–.90). Among counties with ≥1 ID physician (n = 729), only 11.2% had ≥1 waivered ID physician. Conclusions We found an extremely low prevalence and skewed geographic distribution of ID physicians with buprenorphine waivers. Our findings suggest an urgent need to increase the workforce of ID physicians waivered to prescribe buprenorphine and a call for increased integration of OUD education into ID training and continuing medical education. [ABSTRACT FROM AUTHOR]

Background Mass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities. Methods As part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study. Results The pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community). Conclusions Mass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments. [ABSTRACT FROM AUTHOR]

Background Social determinants of health (SDOH) have been associated with coronavirus disease 2019 (COVID-19) outcomes. We examined patterns in COVID-19–related mortality by SDOH and compared these patterns to those for non–COVID-19 mortality. Methods Residents of Ontario, Canada, aged ≥20 years were followed from 1 March 2020 to 2 March 2021. COVID-19–related death was defined as death within 30 days following or 7 days prior to a positive COVID-19 test. Area-level SDOH from the 2016 census included median household income; proportion with diploma or higher educational attainment; proportion essential workers, racially minoritized groups, recent immigrants, apartment buildings, and high-density housing; and average household size. We examined associations between SDOH and COVID-19–related mortality, and non-COVID-19 mortality using cause-specific hazard models. Results Of 11 810 255 individuals, we observed 3880 COVID-19–related deaths and 88 107 non–COVID-19 deaths. After accounting for demographics, baseline health, and other area-level SDOH, the following were associated with increased hazards of COVID-19–related death (hazard ratio [95% confidence interval]: lower income (1.30 [1.04–1.62]), lower educational attainment (1.27 [1.07–1.52]), higher proportions essential workers (1.28 [1.05–1.57]), racially minoritized groups (1.42 [1.08–1.87]), apartment buildings (1.25 [1.07–1.46]), and large vs medium household size (1.30 [1.12–1.50]). Areas with higher proportion racially minoritized groups were associated with a lower hazard of non–COVID-19 mortality (0.88 [0.84–0.92]). Conclusions Area-level SDOH are associated with COVID-19–related mortality after accounting for demographic and clinical factors. COVID-19 has reversed patterns of lower non–COVID-19 mortality among racially minoritized groups. Pandemic responses should include strategies to address disproportionate risks and inequitable coverage of preventive interventions associated with SDOH. [ABSTRACT FROM AUTHOR]

Background Globally, noroviruses cause infections year-round but have recognized winter seasonality in the Northern Hemisphere and yearly variations in incidence. With candidate norovirus vaccines in development, understanding temporal and geographic trends in norovirus disease is important to inform potential vaccination strategies and evaluate vaccine impact. Methods We analyzed data from the National Outbreak Reporting System (NORS) and CaliciNet on single-state norovirus outbreaks that occurred during August 2009–July 2019 in the contiguous United States. We defined norovirus season onset and offset as the weeks by which 10% and 90% of norovirus outbreaks in a surveillance year occurred, respectively, and duration as the difference in weeks between onset and offset. We compared norovirus seasons across surveillance years and geographic regions. Results During August 2009–July 2019, 24 995 single-state norovirus outbreaks were reported to NORS and/or CaliciNet. Nationally, the median norovirus season duration was 24 weeks, with onset occurring between October and December and offset occurring between April and May. Across all years combined, we observed a west-to-east trend in seasonality, with the earliest onset (October) and latest offset (May) occurring in western regions and the latest onset (December) and earliest offset (April) occurring in northeastern regions. Conclusions Timing and duration of the US norovirus season varied annually but generally occurred during October–May. Norovirus wintertime seasonality was less distinct in western regions and was progressively more pronounced moving east. Further understanding the drivers of spatiotemporal dynamics of norovirus could provide insights into factors that promote virus transmission and help guide future interventions. [ABSTRACT FROM AUTHOR]

Background Empiric antibiotic use among hospitalized adults in the United States (US) is largely undescribed. Identifying factors associated with broad-spectrum empiric therapy may inform antibiotic stewardship interventions and facilitate benchmarking. Methods We performed a retrospective cohort study of adults discharged in 2019 from 928 hospitals in the Premier Healthcare Database. "Empiric" gram-negative antibiotics were defined by administration before day 3 of hospitalization. Multivariable logistic regression models with random effects by hospital were used to evaluate associations between patient and hospital characteristics and empiric receipt of broad-spectrum, compared to narrow-spectrum, gram-negative antibiotics. Results Of 8 017 740 hospitalized adults, 2 928 657 (37%) received empiric gram-negative antibiotics. Among 1 781 306 who received broad-spectrum therapy, 30% did not have a common infectious syndrome present on admission (pneumonia, urinary tract infection, sepsis, or bacteremia), surgery, or an intensive care unit stay in the empiric window. Holding other factors constant, males were 22% more likely (adjusted odds ratio [aOR], 1.22 [95% confidence interval, 1.22–1.23]), and all non-White racial groups 6%–13% less likely (aOR range, 0.87–0.94), to receive broad-spectrum therapy. There were significant prescribing differences by region, with the highest adjusted odds of broad-spectrum therapy in the US West South Central division. Even after model adjustment, there remained substantial interhospital variability: Among patients receiving empiric therapy, the probability of receiving broad-spectrum antibiotics varied as much as 34+ percentage points due solely to the admitting hospital (95% interval of probabilities: 43%–77%). Conclusions Empiric gram-negative antibiotic use is highly variable across US regions, and there is high, unexplained interhospital variability. Sex and racial disparities in the receipt of broad-spectrum therapy warrant further investigation. [ABSTRACT FROM AUTHOR]

Background The introduction and adoption of pneumococcal conjugate vaccines (PCVs) into pediatric national immunization programs (NIPs) has led to large decreases in invasive pneumococcal disease (IPD) incidence caused by vaccine serotypes. Despite these reductions, the global IPD burden in children remains significant. Methods We collected serotype-specific IPD data from surveillance systems or hospital networks of all 30 high-income countries that met inclusion criteria. Data sources included online databases, surveillance system reports, and peer-reviewed literature. Percentage of serotyped cases covered were calculated for all countries combined and by PCV type in the pediatric NIP. Results We identified 8012 serotyped IPD cases in children <5 or ≤5 years old. PCV13 serotype IPD caused 37.4% of total IPD cases, including 57.1% and 25.2% for countries with PCV10 or PCV13 in the pediatric NIP, respectively, most commonly due to serotypes 3 and 19A (11.4% and 13.3%, respectively, across all countries). In PCV10 countries, PCV15 and PCV20 would cover an additional 45.1% and 55.6% of IPD beyond serotypes contained in PCV10, largely due to coverage of serotype 19A. In PCV13 countries, PCV15 and PCV20 would cover an additional 10.6% and 38.2% of IPD beyond serotypes contained in PCV13. The most common IPD serotypes covered by higher valency PCVs were 10A (5.2%), 12F (5.1%), and 22F and 33F (3.5% each). Conclusions Much of the remaining IPD burden is due to serotypes included in PCV15 and PCV20. The inclusion of these next generation PCVs into existing pediatric NIPs may further reduce the incidence of childhood IPD. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) infection rates among US blood donors have been well characterized; however, few studies evaluated HCV genotypes among blood donors. Monitoring trends in disease and demographic patterns contributes to understanding the safety of the blood supply. We examined the demographic characteristics and distribution of HCV genotypes/subgenotypes for nearly a 16-year period among blood donors confirmed positive for HCV RNA but antibody negative (defined as nucleic acid testing [NAT] yield). Methods A retrospective assessment of demographic characteristics and testing data was used to determine temporal trends and geographical distribution of HCV genotypes/subgenotypes among American Red Cross blood donors confirmed positive as HCV-NAT yield. Results From 2003–2018, 343 donors (0.38/100 000 donations; 95% CI,.35–.43) were confirmed positive as HCV-NAT–yield cases. Temporal analysis revealed a significant increase in HCV-NAT–yield cases of 54.1% between 2009 and 2014 (P =.014), followed by a significant decline of 31.4% between 2015 and 2018 (P =.002). Significantly more HCV-NAT–yield cases were detected among first-time donors, non-Hispanic Whites, donors aged 20–29 years, equally likely to be males as females, with the highest frequency in the South (0.52/100 000 donations). Subgenotype 1a (49.6%) was most frequent, followed by 3a (18.7%), 2b (12.5%), 1b (8.5%), and 2a (1.7%). Conclusions Voluntary nonremunerated blood donors are at low risk for HCV infection. Since 2015, the frequency of HCV-NAT–yield cases decreased despite an increase in acute HCV infection in the general population. HCV subgenotypes 1a and 3a continue to remain predominant among US blood donors with recent HCV infection. [ABSTRACT FROM AUTHOR]

Background Strongyloides stercoralis is considered to be historically endemic in Appalachia and the American South, but recent surveillance data, especially data evaluating strongyloidiasis associated with hospitalization, are lacking in most parts of the United States. Methods We performed a population-based retrospective analysis on strongyloidiasis using the National Inpatient Sample from 2003 to 2018. Geographic distribution of strongyloidiasis associated hospitalization was assessed. Logistic regression was used to identify risk factors associated with strongyloidiasis. Results We identified 6931 hospitalizations associated with strongyloidiasis during the study period (11.8 per million hospitalizations). The rate of strongyloidiasis was highest in the Northeast US region, including the Middle Atlantic division (47.1 cases per million population; adjusted odds ratio, 2.00 [95% confidence interval: 1.58–2.53]), and the East South Central division (27.5 cases per million; adjusted odds ratio, 2.77 [2.02–3.80]). Older age, male sex, nonwhite race/ethnicity (particularly Hispanic and Asian), nonprivate insurance, and residence in neighborhoods with low median income were also associated with strongyloidiasis. Immunocompromising conditions, particularly human immunodeficiency virus infection, were present in 41.3% of hospitalizations with strongyloidiasis. In-hospital death occurred in 7.8% of patients with strongyloidiasis-associated hospitalization. Conclusions Strongyloidiasis-associated hospitalization is rare in the United States but can be associated with increased mortality rate/mortality risk. It occurs more frequently in poor and marginalized populations. Immunocompromised conditions were common among hospitalized patients with strongyloidiasis. Enhanced surveillance efforts are needed to inform health policies for improving the health of at-risk populations. [ABSTRACT FROM AUTHOR]

Background Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis , with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a potential biowarfare agent. Methods We completed a systematic review for clinical and demographic characteristics of adults and children hospitalized with anthrax (cutaneous, inhalation, ingestion, injection [from contaminated heroin], primary meningitis) abstracted from published case reports, case series, and line lists in English from 1880 through 2018, assessing treatment impact by type and severity of disease. We analyzed geographic distribution, route of infection, exposure to anthrax, and incubation period. Results Data on 764 adults and 167 children were reviewed. Most cases reported for 1880 through 1915 were from Europe; those for 1916 through 1950 were from North America; and from 1951 on, cases were from Asia. Cutaneous was the most common form of anthrax for all populations. Since 1960, adult anthrax mortality has ranged from 31% for cutaneous to 90% for primary meningitis. Median incubation periods ranged from 1 day (interquartile range [IQR], 0–4) for injection to 7 days (IQR, 4–9) for inhalation anthrax. Most patients with inhalation anthrax developed pleural effusions and more than half with ingestion anthrax developed ascites. Treatment and critical care advances have improved survival for those with systemic symptoms, from approximately 30% in those untreated to approximately 70% in those receiving antimicrobials or antiserum/antitoxin. Conclusions This review provides an improved evidence base for both clinical care of individual anthrax patients and public health planning for wide-area aerosol releases of B. anthracis spores. [ABSTRACT FROM AUTHOR]

Background Although human case numbers of variant influenza viruses have increased worldwide, the epidemiology of human cases and human-to-human transmissibility of different variant viruses remain uncertain. Methods We used descriptive statistics to summarize the epidemiologic characteristics of variant virus infections. The hospitalization rate, case-fatality, and hospitalization-fatality risks were used to assess disease severity. Transmissibility of variant viruses between humans was determined by the effective reproductive number (R e ) and probability of infection following exposure to human cases. Results We identified 707 naturally infected cases of variant viruses from 1959 to 2021, and their spatiotemporal/demographic characteristics changed across subtypes. The clinical severity of cases of variant viruses was generally mild; patients older than 18 years with underlying conditions were associated with hospitalization. Of 69 clusters of human infections with variant viruses (median cluster size: 2), the upper limit of R e was 0.09 (H1N1v, H1N2v, and H3N2v: 0.20 vs 0.18 vs 0.05), whereas it was not significantly different from the pooled estimates for avian influenza A(H7N9) and A(H5N1) viruses (0.10). Moreover, contacts of H5N1 cases (15.7%) had a significantly higher probability of infection than contacts of individuals with H7N9 (4.2%) and variant virus infections (4.2%–7.2%). Conclusions The epidemiology of cases of variant viruses varied across time periods, geographical regions, and subtypes during 1959–2021. The transmissibility of different variant viruses between humans remains limited. However, given the continuous evolution of viruses and the rapidly evolving epidemiology of cases of variant viruses, improving the surveillance systems for human variant virus infections is needed worldwide. [ABSTRACT FROM AUTHOR]

Background Among antiretroviral therapy (ART)–treated people with human immunodeficiency virus (PWH), persistent systemic immune activation contributes to atherogenesis atherosclerotic, cardiovascular disease (CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH. Methods Leveraging baseline Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) data, we evaluated factors associated with soluble CD14 (sCD14) and oxidized low-density lipoprotein (oxLDL). Results The primary analysis cohort included 4907 participants from 5 global-burden-of-disease regions (38% female, 48% Black, median age 50 years). In fully adjusted models for sCD14, female sex and White race (among those in high-income regions) were associated with higher sCD14 levels, while higher body mass index (BMI) and current use of nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, White race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a subanalysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels. Conclusions Factors associated with sCD14 and oxLDL, 2 key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (eg, statins) and behavioral modifications influence sCD14 and oxLDL and the extent to which dampening of these markers mediates CVD-protective effects. Clinical Trials Registration NCT0234429. [ABSTRACT FROM AUTHOR]

Background Reductions in tuberculosis (TB) transmission have been instrumental in lowering TB incidence in the United States. Sustaining and augmenting these reductions are key public health priorities. Methods We fit mechanistic transmission models to distributions of genotype clusters of TB cases reported to the Centers for Disease Control and Prevention during 2012–2016 in the United States and separately in California, Florida, New York, and Texas. We estimated the mean number of secondary cases generated per infectious case (R 0) and individual-level heterogeneity in R 0 at state and national levels and assessed how different definitions of clustering affected these estimates. Results In clusters of genotypically linked TB cases that occurred within a state over a 5-year period (reference scenario), the estimated R 0 was 0.29 (95% confidence interval [CI],.28–.31) in the United States. Transmission was highly heterogeneous; 0.24% of simulated cases with individual R 0  >10 generated 19% of all recent secondary transmissions. R 0 estimate was 0.16 (95% CI,.15–.17) when a cluster was defined as cases occurring within the same county over a 3-year period. Transmission varied across states: estimated R 0 s were 0.34 (95% CI,.3–.4) in California, 0.28 (95% CI,.24–.36) in Florida, 0.19 (95% CI,.15–.27) in New York, and 0.38 (95% CI,.33–.46) in Texas. Conclusions TB transmission in the United States is characterized by pronounced heterogeneity at the individual and state levels. Improving detection of transmission clusters through incorporation of whole-genome sequencing and identifying the drivers of this heterogeneity will be essential to reducing TB transmission. [ABSTRACT FROM AUTHOR]

Background We assess if state-issued nonpharmaceutical interventions (NPIs) are associated with reduced rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as measured through anti-nucleocapsid (anti-N) seroprevalence, a proxy for cumulative prior infection that distinguishes seropositivity from vaccination. Methods Monthly anti-N seroprevalence during 1 August 2020 to 30 March 2021 was estimated using a nationwide blood donor serosurvey. Using multivariable logistic regression models, we measured the association of seropositivity and state-issued, county-specific NPIs for mask mandates, gathering bans, and bar closures. Results Compared with individuals living in a county with all three NPIs in place, the odds of having anti-N antibodies were 2.2 (95% confidence interval [CI]: 2.0–2.3) times higher for people living in a county that did not have any of the 3 NPIs, 1.6 (95% CI: 1.5–1.7) times higher for people living in a county that only had a mask mandate and gathering ban policy, and 1.4 (95% CI: 1.3–1.5) times higher for people living in a county that had only a mask mandate. Conclusions Consistent with studies assessing NPIs relative to COVID-19 incidence and mortality, the presence of NPIs were associated with lower SARS-CoV-2 seroprevalence indicating lower rates of cumulative infections. Multiple NPIs are likely more effective than single NPIs. [ABSTRACT FROM AUTHOR]

Background We sought to explore multinational differences in functional status by global burden of disease (GBD) regions in the REPRIEVE cohort. Methods REPRIEVE is a prospective, double-blind, randomized, placebo-controlled, multicenter, phase III primary cardiovascular prevention study of pitavastatin calcium vs placebo among people with human immunodeficiency virus (HIV, PWH) ages 40–75 on antiretroviral therapy (ART). GBD super regions were defined using World Health Organization classifications. Participants were categorized by impairment on the Duke Activity Status Instrument (DASI: none, some, moderate, severe). Logistic regression models examined risk factors and GBD regions associated with functional impairment. The association between functional impairment and cardiometabolic risk was also explored. Results Of 7736 participants, the majority were from high-income countries (n = 4065), were male (65%), and had received ART for ≥ 10 years. The median DASI score was 58.2 (interquartile range [IQR] 50.2, 58.2); 36% reported at least some impairment. In adjusted analyses, functional impairment was significantly more frequent among participants from Southeast/East Asia. Other factors associated with greater impairment included female sex, Black race, older age, current/former smoking, higher body mass index, use of ART for ≥ 10 years, and select ART regimens; differences were seen in risks across GBD regions. Functional impairment was associated with increased cardiometabolic risk. Conclusions Over 1/3 of middle-aged and older PWH in a global cohort across diverse GBD regions demonstrate functional impairments. The associations between DASI and cardiometabolic risk suggest that a measure of functional status may improve risk prediction; these longitudinal associations will be further investigated over REPRIEVE trial follow-up. [ABSTRACT FROM AUTHOR]

Background Accurate human immunodeficiency virus (HIV) risk assessment can guide optimal HIV prevention. We evaluated the performance of risk prediction models incorporating geospatial measures. Methods We developed and validated HIV risk prediction models in a population-based cohort in South Africa. Individual-level covariates included demographic and sexual behavior measures, and geospatial covariates included community HIV prevalence and viral load estimates. We trained models on 2012–2015 data using LASSO Cox models and validated predictions in 2016–2019 data. We compared full models to simpler models restricted to only individual-level covariates or only age and geospatial covariates. We compared the spatial distribution of predicted risk to that of high incidence areas (≥ 3/100 person-years). Results Our analysis included 19 556 individuals contributing 44 871 person-years and 1308 seroconversions. Incidence among the highest predicted risk quintile using the full model was 6.6/100 person-years (women) and 2.8/100 person-years (men). Models using only age group and geospatial covariates had similar performance (women: AUROC = 0.65, men: AUROC = 0.71) to the full models (women: AUROC = 0.68, men: AUROC = 0.72). Geospatial models more accurately identified high incidence regions than individual-level models; 20% of the study area with the highest predicted risk accounted for 60% of the high incidence areas when using geospatial models but only 13% using models with only individual-level covariates. Conclusions Geospatial models with no individual measures other than age group predicted HIV risk nearly as well as models that included detailed behavioral data. Geospatial models may help guide HIV prevention efforts to individuals and geographic areas at highest risk. [ABSTRACT FROM AUTHOR]

Background Measles elimination (interruption of endemic measles virus transmission) in the United States was declared in 2000; however, the number of cases and outbreaks have increased in recent years. We characterized the epidemiology of measles outbreaks and measles transmission patterns after elimination to identify potential gaps in the US measles control program. Methods We analyzed national measles notification data from 1 January 2001 to 31 December 2019. We defined measles infection clusters as single cases (isolated cases not linked to additional cases), 2-case clusters, or outbreaks with ≥3 linked cases. We calculated the effective reproduction number (R) to assess changes in transmissibility and reviewed molecular epidemiology data. Results During 2001–2019, a total of 3873 measles cases, including 747 international importations, were reported in the United States; 29% of importations were associated with outbreaks. Among 871 clusters, 69% were single cases and 72% had no spread. Larger and longer clusters were reported since 2013, including 7 outbreaks with >50 cases lasting >2 months, 5 of which occurred in known underimmunized, close-knit communities. No measles lineage circulated in a single transmission chain for >12 months. Higher estimates of R were noted in recent years, although R remained below the epidemic threshold of 1. Conclusions Current epidemiology continues to support the interruption of endemic measles virus transmission in the United States. However, larger and longer outbreaks in recent postelimination years and emerging trends of increased transmission in underimmunized communities emphasize the need for targeted approaches to close existing immunity gaps and maintain measles elimination. [ABSTRACT FROM AUTHOR]

Background Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. Methods A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. Results Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78–23.33), presence of underlying disease (1.33; 1.19–1.49), worse case severity (severe: 3.86; 3.15–4.73; critical: 11.34; 9.22–13.95), and near-epicenter region (Hubei: 2.64; 2.11–3.30; Wuhan: 6.35; 5.04–8.00). CFR increased from 0.35% (30–39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). Conclusions Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed. [ABSTRACT FROM AUTHOR]

Background To inform the World Health Organization's full value of vaccine assessment for group B Streptococcus (GBS) vaccines, a rapid literature appraisal was conducted to inform the operationalization of maternal GBS vaccination. We found limited published information on stakeholder perceptions of the public health importance of GBS disease and vaccination, and we therefore undertook a multicountry survey. Methods An online survey was conducted in late 2019 to collect information on stakeholders' awareness of GBS disease and the priority accorded to vaccination. The survey was distributed by email to 395 representatives of national pediatric, gynecology, and obstetrics associations, national immunization technical advisory groups (NITAGs), national regulatory agencies, academia, and United Nations organizations. Results Among 101 survey respondents from 66 countries, 36% were pediatricians, 25% obstetricians/gynecologists, 21% immunization specialists, and 18% other public health specialists. More than half (58%) of respondents reported being familiar with GBS disease as a public health problem; familiarity decreased by country income level. Knowledge of GBS disease was greatest in the Americas (68%) and Europe (66%) and lowest in Asia (13%–38%). Perception of GBS disease as a public health problem was highest among pediatricians (71%) and lowest among public health policy makers and NITAG members (30%) across country groupings. Approximately half of respondents (49%) considered the introduction of a GBS vaccine as a priority. Conclusions The information obtained will inform the appropriate packaging and presentation of information to address stakeholder perceptions and promote evidence-based decision making on GBS vaccination. [ABSTRACT FROM AUTHOR]

Background Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with human immunodeficiency virus (PLHIV) who were lost to follow-up (LTFU) during 2014–2017 at ART programs in Southern Africa. Methods We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records and used a standardized protocol to trace a weighted random sample of PLHIV who were LTFU in 8 ART programs in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, 2017–2019. We ascertained vital status and identified predictors of mortality using logistic regression, adjusted for sex, age, time on ART, time since LTFU, travel time, and urban or rural setting. Results Among 3256 PLHIV, 385 (12%) were wrongly categorized as LTFU and 577 (17%) had missing contact details. We traced 2294 PLHIV (71%) by phone calls, home visits, or both: 768 (34% of 2294) were alive and in care, including 385 (17%) silent transfers to another clinic; 528 (23%) were alive without care or unknown care; 252 (11%) had died. Overall, the status of 1323 (41% of 3256) PLHIV remained unknown. Mortality was higher in men than women, higher in children than in young people or adults, and higher in PLHIV who had been on ART <1 year or LTFU ≥1 year and those living farther from the clinic or in rural areas. Results were heterogeneous across sites. Conclusions Our study highlights the urgent need for better medical record systems at HIV clinics and rapid tracing of PLHIV who are LTFU. [ABSTRACT FROM AUTHOR]

Background Disparities were marked in previous pandemics, usually with higher attack rates reported for those in lower socioeconomic positions and for ethnic minorities. Methods We examined characteristics of laboratory-confirmed coronavirus disease 2019 (COVID-19) cases in Hong Kong, assessed associations between incidence and population-level characteristics at the level of small geographic areas, and evaluated relations between socioeconomics and work-from-home (WFH) arrangements. Results The largest source of COVID-19 importations switched from students studying overseas in the second wave to foreign domestic helpers in the third. The local cases were mostly individuals not in formal employment (retirees and homemakers) and production workers who were unable to WFH. For every 10% increase in the proportion of population employed as executives or professionals in a given geographic region, there was an 84% (95% confidence interval [CI], 1–97%) reduction in the incidence of COVID-19 during the third wave. In contrast, in the first 2 waves, the same was associated with 3.69 times (95% CI, 1.02–13.33) higher incidence. Executives and professionals were more likely to implement WFH and experienced frequent changes in WFH practice compared with production workers. Conclusions Consistent findings on the reversed socioeconomic patterning of COVID-19 burden between infection waves in Hong Kong in both individual- and population-level analyses indicated that risks of infections may be related to occupations involving high exposure frequency and WFH flexibility. Contextual determinants should be taken into account in policy planning aiming at mitigating such disparities. [ABSTRACT FROM AUTHOR]

Background We sought to determine if racial differences in influenza vaccination among nursing home (NH) residents during the 2008–2009 influenza season persisted in 2018–2019. Methods We conducted a cross-sectional study of NHs certified by the Centers for Medicare & Medicaid Services during the 2018–2019 influenza season in US states with ≥1% Black NH residents and a White–Black gap in influenza vaccination of NH residents (N = 2 233 392) of at least 1 percentage point (N = 40 states). NH residents during 1 October 2018 through 31 March 2019 aged ≥18 years and self-identified as being of Black or White race were included. Residents' influenza vaccination status (vaccinated, refused, and not offered) was assessed. Multilevel modeling was used to estimate facility-level vaccination status and inequities by state. Results The White–Black gap in influenza vaccination was 9.9 percentage points. In adjusted analyses, racial inequities in vaccination were more prominent at the facility level than at the state level. Black residents disproportionately lived in NHs that had a majority of Blacks residents, which generally had the lowest vaccination. Inequities were most concentrated in the Midwestern region, also the most segregated. Not being offered the vaccine was negligible in absolute percentage points between White residents (2.6%) and Black residents (4.8%), whereas refusals were higher among Black (28.7%) than White residents (21.0%). Conclusions The increase in the White–Black vaccination gap among NH residents is occurring at the facility level in more states, especially those with the most segregation. [ABSTRACT FROM AUTHOR]

Background Direct-acting antivirals (DAAs) are becoming accessible in sub-Saharan Africa. This study examined the effectiveness of DAAs in patients treated through the Rwandan national health system and identified factors associated with treatment outcomes. Methods This retrospective study used data from the national hepatitis C virus (HCV) program for patients who initiated DAAs between November 2015 and March 2017. Sustained virological response at 12 weeks after treatment (SVR12) was the primary outcome. Logistic regression models were fit to estimate the relationship between patients' clinical and demographic characteristics and treatment outcome. Results 894 patients started treatment during the study period; 590 completed treatment and had SVR12 results. Among the 304 patients without SVR12 results, 48 were lost to follow-up and 256 had no SVR12 results but clinical data indicated they likely completed treatment; these patients were classified as nonvirological failure because viral clearance could not be determined. In a per-protocol analysis of 590 patients with SVR12 results, SVR12 was achieved in 540 (92%), and virological failure occurred in 50 (8%). Pretreatment HCV RNA above the median split was associated with virological failure. Intention-to-treat analyses including all patients showed that SVR12 was achieved in 540 (60%), with nonvirological failure in 304 (34%) and virological failure in 50 (6%). Patients in Western Province were more likely to experience nonvirological failure than patients in Kigali, likely owing to the 5–7-hour travel required to access testing and treatment. Conclusions DAAs were effective when implemented through the Rwandan national health system. Decentralization and enhanced financing are underway in Rwanda, which could improve access to treatment and follow-up as the country prepares for HCV elimination. [ABSTRACT FROM AUTHOR]

Background To highlight geographic differences and the socio-structural determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positivity within Los Angeles County (LAC). Methods A geographic information system was used to integrate, map, and analyze SARS-CoV-2 testing data reported by the LAC Department of Public Health and data from the American Community Survey. Structural determinants included race/ethnicity, poverty, insurance status, education, and population and household density. We examined which factors were associated with positivity rates, using a 5% test positivity threshold, with spatial analysis and spatial regression. Results Between 1 March and 30 June 2020 there were 843 440 SARS-CoV-2 tests and 86 383 diagnoses reported, for an overall positivity rate of 10.2% within the study area. Communities with high proportions of Latino/a residents, those living below the federal poverty line, and with high household densities had higher crude positivity rates. Age- adjusted diagnosis rates were significantly associated with the proportion of Latino/as, individuals living below the poverty line, and population and household density. Conclusions There are significant local variations in test positivity within LAC and several socio-structural determinants contribute to ongoing disparities. Public health interventions, beyond shelter in place, are needed to address and target such disparities. [ABSTRACT FROM AUTHOR]

Background Identifying risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could help health systems improve testing and screening strategies. The aim of this study was to identify demographic factors, comorbid conditions, and symptoms independently associated with testing positive for SARS-CoV-2. Methods This was an observational cross-sectional study at the Veterans Health Administration, including persons tested for SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR) between 28 February and 14 May 2020. Associations between demographic characteristics, diagnosed comorbid conditions, and documented symptoms with testing positive for SARS-CoV-2 were measured. Results Of 88 747 persons tested, 10 131 (11.4%) were SARS-CoV-2 PCR positive. Positivity was associated with older age (≥80 vs <50 years: adjusted odds ratio [aOR], 2.16 [95% confidence interval {CI}, 1.97–2.37]), male sex (aOR, 1.45 [95% CI, 1.34–1.57]), regional SARS-CoV-2 burden (≥2000 vs <400 cases/million: aOR, 5.43 [95% CI, 4.97–5.93]), urban residence (aOR, 1.78 [95% CI, 1.70–1.87]), black (aOR, 2.15 [95% CI, 2.05–2.26]) or American Indian/Alaska Native Hawaiian/Pacific Islander (aOR, 1.26 [95% CI, 1.05–1.52]) vs white race, and Hispanic ethnicity (aOR, 1.52 [95% CI, 1.40–1.65]). Obesity and diabetes were the only 2 medical conditions associated with testing positive. Documented fevers, chills, cough, and diarrhea were also associated with testing positive. The population attributable fraction of positive tests was highest for geographic location (35.3%), followed by demographic variables (27.1%), symptoms (12.0%), obesity (10.5%), and diabetes (0.4%). Conclusions The majority of positive SARS-CoV-2 tests were attributed to geographic location, demographic characteristics, and obesity, with a minor contribution of chronic comorbid conditions. [ABSTRACT FROM AUTHOR]

Background The United States has been heavily impacted by the coronavirus disease 2019 (COVID-19) pandemic. Understanding microlevel patterns in US rates of COVID-19 can inform specific prevention strategies. Methods Using a negative binomial mixed-effects regression model, we evaluated the associations between a broad set of US county-level sociodemographic, economic, and health status–related characteristics and cumulative rates of laboratory-confirmed COVID-19 cases and deaths between 22 January 2020 and 31 August 2020. Results Rates of COVID-19 cases and deaths were higher in US counties that were more urban or densely populated or that had more crowded housing, air pollution, women, persons aged 20–49 years, racial/ethnic minorities, residential housing segregation, income inequality, uninsured persons, diabetics, or mobility outside the home during the pandemic. Conclusions To our knowledge, this study provides results from the most comprehensive multivariable analysis of county-level predictors of rates of COVID-19 cases and deaths conducted to date. Our findings make clear that ensuring that COVID-19 preventive measures, including vaccines when available, reach vulnerable and minority communities and are distributed in a manner that meaningfully disrupts transmission (in addition to protecting those at highest risk of severe disease) will likely be critical to stem the pandemic. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P  < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P  < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines. [ABSTRACT FROM AUTHOR]

Background Integrated community case management (iCCM) of malaria complements public health services to improve access to timely diagnosis and treatment of malaria. ICCM relies on standardized test-and-treat algorithms implemented by community health workers using malaria rapid diagnostic tests (RDTs). However, due to a changing epidemiology of fever causes in Africa, positive RDT results might not correctly reflect malaria. In this study, we modeled diagnostic predictive values for all malaria-endemic African regions as an indicator of the programmatic usefulness of RDTs in iCCM campaigns on malaria. Methods Positive predictive values (PPVs) and negative predictive values (NPVs) of RDTs for clinical malaria were modeled. Assay-specific performance characteristics stem from the Cochrane Library and data on the proportion of malaria-attributable fevers among African febrile children aged <5 years were used as prevalence matrix. Results Average country-level PPVs vary considerably. Ethiopia had the lowest PPVs (histidine-rich protein II [HRP2] assay, 17.35%; parasite lactate dehydrogenase [pLDH] assay, 39.73%), and Guinea had the highest PPVs (HRP2 assay, 95.32%; pLDH assay, 98.46%). On the contrary, NPVs were above 90% in all countries (HRP2 assay, ≥94.87%; pLDH assay, ≥93.36%). Conclusions PPVs differed considerably within Africa when used to screen febrile children, indicating unfavorable performance of RDT-based test-and-treat algorithms in low-PPV settings. This suggests that the administration of antimalarials alone may not constitute causal treatment in the presence of a positive RDT result for a substantial proportion of patients, particularly in low-PPV settings. Therefore, current iCCM algorithms should be complemented by information on other setting-specific major causes of fever. [ABSTRACT FROM AUTHOR]

Background Despite the demonstrated impact of pneumococcal vaccine (PCV) implementation on otitis media (OM), demonstration of real-life serotype-specific effectiveness of the 7-valent and 13-valent PCVs (PCV7 and PCV13) is lacking owing to the paucity of culture-positive cases. Furthermore, prelicensure PCV13 efficacy against OM was not studied. Methods The study was conducted from October 2009 to July 2013. Case patients were children aged 5–35 months with OM (mostly complex OM [recurrent/nonresponsive, spontaneously draining, chronic with effusion]) from whom middle-ear fluid culture was obtained; controls were contemporary children with rotavirus-negative gastroenteritis in a prospective population-based rotavirus surveillance, from the same age group with similar ethnic distribution and geographic location. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio using unconditional logistic regression, adjusting for time since PCV implementation, age, and ethnicity. Results A total of 223 case patients and 1370 controls were studied. Serotypes 19F and 19A together caused 56.1% of all vaccine-type (VT) OM. VE of ≥2 PCV doses in children aged 5–35 months was demonstrated as follows: PCV7 against OM due to PCV7 serotypes, 57.2% (95% confidence interval, 6.0%–80.5%); PCV13 against OM due to PCV13 serotypes, 77.4% (53.3%–92.1%); PCV13 against OM due to the 6 additional non-PCV7 serotypes 67.4% (17.6%–87.1%); PCV13 against OM due to serotype 19F, 91.3% (1.4%–99.2%); and PCV13 against OM due to serotype 3, 85.2% (23.9%–98.4%). PCV7 and PCV13 VE against OM due to serotype 19A in children aged 12–35 months was 72.4% (95% confidence interval, 6.2%–91.9%) and 94.6% (33.9%–99.6%), respectively. Conclusions PCV7 and PCV13 were effective against complex OM caused by the targeted serotypes. [ABSTRACT FROM AUTHOR]

Background New drug development for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) is critical. Challenges remain in the conduct of HABP/VABP trials, especially in the contexts of enrollment, endpoints, nonstudy antibacterial drug therapy, and antimicrobial resistance. Methods Four Phase 3 noninferiority trials (n = 2433 participants) submitted to the Food and Drug Administration after 2015 were analyzed for enrollment statistics, participant characteristics associated with 28-day all-cause mortality (ACM), microbiology, and receipt of nonstudy antibacterial drugs. All trials primarily enrolled patients with gram-negative bacterial infections. Results The mean trial length was 2.7 years and the mean recruitment rate was 0.17 participants/site/month. ACM at 28 days was 17.1% and was higher among participants diagnosed with ventilated HABP (31.9%) or VABP (19.0%) than nonventilated HABP (9.9%). VABP participants tended to be younger, less likely to have chronic obstructive pulmonary disease, and more likely to have previously sustained an injury. Age, South American residence, diagnosis of ventilated HABP or VABP, and Acinetobacter baumannii infection were all associated with 28-day ACM in a multivariate logistic regression model. Infection by A. baumannii was most common in Eastern European and Asia/Pacific participants, and Eastern European isolates exhibited the highest levels of meropenem resistance. Concomitant nonstudy antibacterial drug therapy most commonly included beta-lactams and was initiated earliest in Western Europe. Conclusion This analysis of recent trials may assist in trial considerations for HABP/VABP development programs and promote needed antibacterial drug development for patients with serious infections. [ABSTRACT FROM AUTHOR]

Background Research suggests that human immunodeficiency virus (HIV)–positive individuals with a sexually transmitted infection (STI) may be at increased risk of transmitting HIV to someone else through unprotected sex. The primary aim of the analysis is to identify the high-risk geographic areas of transmission of coinfections and factors that may be associated with poor outcomes of viral suppression within these higher-risk geographic areas, thus important in transmission prevention. Methods We used surveillance data reported by all providers and laboratories in the District of Columbia (DC). Applied discrete Poisson scan model in SaTScan to identify the geographic areas. The relative risk (RR) for the scan statistic was calculated based on events inside the cluster, and P values evaluated statistical significance. We used multinomial logistical regression to explore care and demographical characteristics associated with being virally unsuppressed within and outside the geographic areas. Results The coinfected areas (RR, >1; P <.001) were located in the tracts of central and southern DC. Black population (RR, 3.154 [95% confidence interval {CI}, 1.736–5.729]), age 13–19 years (RR, 4.598 [95% CI, 3.176–6.657]), repeat STIs (RR, 1.387 [95% CI, 1.096–1.754]), and not retained in care (RR, 2.546 [95% CI, 1.997–3.245]) were found to be at higher risk of being virally unsuppressed within the coinfected clusters. Those with unknown linkages were found to be at higher risk of being virally unsuppressed outside the coinfected clusters (RR, 5.162 [95% CI, 2.289–11.640]). Conclusions This is DC's first effort to identify the geographic core areas of coinfections and factors that may be sustaining them. These results will be used by the health department to plan for prevention-intervention strategies. This model be replicated by any local jurisdiction similar. [ABSTRACT FROM AUTHOR]

Background Due to spatial heterogeneity in onchocerciasis transmission, the duration of ivermectin mass drug administration (MDA) required for eliminating onchocerciasis will vary within endemic areas and the occurrence of transmission "hotspots" is inevitable. The geographical scale at which stop-MDA decisions are made will be a key driver in how rapidly national programs can scale down active intervention upon achieving the epidemiological targets for elimination. Methods We used 2 onchocerciasis models (EPIONCHO-IBM and ONCHOSIM) to predict the likelihood of achieving elimination by 2030 in Africa, accounting for variation in preintervention endemicity levels and histories of ivermectin treatment. We explore how decision making at contrasting geographical scales (community vs larger scale "project") changes projections on populations still requiring MDA or transitioning to post-treatment surveillance. Results The total population considered grows from 118 million people in 2020 to 136 million in 2030. If stop-MDA decisions are made at project level, the number of people requiring treatment declines from 69–118 million in 2020 to 59–118 million in 2030. If stop-MDA decisions are made at community level, the numbers decline from 23–81 million in 2020 to 15–63 million in 2030. The lower estimates in these prediction intervals are based on ONCHOSIM, the upper limits on EPIONCHO-IBM. Conclusions The geographical scale at which stop-MDA decisions are made strongly determines how rapidly national onchocerciasis programs can scale down MDA programs. Stopping in portions of project areas or transmission zones would free up human and economic resources. [ABSTRACT FROM AUTHOR]

Maps of the geographical variation in prevalence play an important role in large-scale programs for the control of neglected tropical diseases. Precontrol mapping is needed to establish the appropriate control intervention in each area of the country in question. Mapping is also needed postintervention to measure the success of control efforts. In the absence of comprehensive disease registries, mapping efforts can be informed by 2 kinds of data: empirical estimates of local prevalence obtained by testing individuals from a sample of communities within the geographical region of interest, and digital images of environmental factors that are predictive of local prevalence. In this article, we focus on the design and analysis of impact surveys, that is, prevalence surveys that are conducted postintervention with the aim of informing decisions on what further intervention, if any, is needed to achieve elimination of the disease as a public health problem. We show that geospatial statistical methods enable prevalence surveys to be designed and analyzed as efficiently as possible so as to make best use of hard-won field data. We use 3 case studies based on data from soil-transmitted helminth impact surveys in Kenya, Sierra Leone, and Zimbabwe to compare the predictive performance of model-based geostatistics with methods described in current World Health Organization (WHO) guidelines. In all 3 cases, we find that model-based geostatistics substantially outperforms the current WHO guidelines, delivering improved precision for reduced field-sampling effort. We argue from experience that similar improvements will hold for prevalence mapping of other neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Background Tremendous progress towards elimination of trachoma as a public health problem has been made. However, there are areas where the clinical indicator of disease, trachomatous inflammation—follicular (TF), remains prevalent. We quantify the progress that has been made, and forecast how TF prevalence will evolve with current interventions. We also determine the probability that a district is a transmission-hotspot based on its TF prevalence (ie, reproduction number greater than one). Methods Data on trachoma prevalence come from the GET2020 global repository organized by the World Health Organization and the International Trachoma Initiative. Forecasts of TF prevalence and the percent of districts with local control is achieved by regressing the coefficients of a fitted exponential distribution for the year-by-year distribution of TF prevalence. The probability of a district being a transmission-hotspot is extrapolated from the residuals of the regression. Results Forecasts suggest that with current interventions, 96.5% of surveyed districts will have TF prevalence among children aged 1–9 years <5% by 2030 (95% CI: 86.6%–100.0%). Districts with TF prevalence < 20% appear unlikely to be transmission-hotspots. However, a district having TF prevalence of over 28% in 2016–2019 corresponds to at least 50% probability of being a transmission-hotspot. Conclusions Sustainable control of trachoma appears achievable. However there are transmission-hotspots that are not responding to annual mass drug administration of azithromycin and require enhanced treatment in order to reach local control. [ABSTRACT FROM AUTHOR]

Background Understanding the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for public health control efforts. Social, demographic, and political characteristics at the United States (US) county level might be associated with changes in SARS-CoV-2 case incidence. Methods We conducted a retrospective analysis of the relationship between the change in reported SARS-CoV-2 case counts at the US county level during 1 June–30 June 2020 and social, demographic, and political characteristics of the county. Results Of 3142 US counties, 1023 were included in the analysis: 678 (66.3%) had increasing and 345 (33.7%) nonincreasing SARS-CoV-2 case counts between 1 June and 30 June 2020. In bivariate analysis, counties with increasing case counts had a significantly higher Social Deprivation Index (median, 48 [interquartile range {IQR}, 24–72]) than counties with nonincreasing case counts (median, 40 [IQR, 19–66]; P =.009). Counties with increasing case counts were significantly more likely to be metropolitan areas of 250 000–1 million population (P <.001), to have a higher percentage of black residents (9% vs 6%; P =.013), and to have voted for the Republican presidential candidate in 2016 by a ≥10-point margin (P =.044). In the multivariable model, metropolitan areas of 250 000–1 million population, higher percentage of black residents, and a ≥10-point Republican victory were independently associated with increasing case counts. Conclusions Increasing case counts of SARS-CoV-2 in the US during June 2020 were associated with a combination of sociodemographic and political factors. Addressing social disadvantage and differential belief systems that may correspond with political alignment will play a critical role in pandemic control. [ABSTRACT FROM AUTHOR]

Background Population-based studies on the mortality burden of nontuberculous mycobacteria (NTM) infection are lacking. We compared the long-term mortality of NTM-infected patients with tuberculosis (TB)-patients and the general population, and investigated mortality-associated factors. Methods We analyzed nationwide-data from the Korean National Health Insurance and Korea-Statistical Office between 2002 and 2017. NTM infection was identified using the International Classification of Disease, Tenth Revision code, with one-to-one matching to TB patients and general population controls. Results A total of 530 401 individuals were analyzed, including 183 267 with NTM infections; 166 666 with TB; and 180 468 controls. The overall 6-, 10-, and 14-year cumulative survival probabilities in the NTM group were 86.3%, 80.8%, and 77.1%, respectively, which were significantly lower than those of the TB or control groups (log-rank P <.0001). In cases of NTM and TB coinfection, the overall 6-, 10-, and 14-year cumulative survival probabilities were 75.1%, 65.4%, and 57.0%, respectively. Multivariable analysis indicated that old age, male gender, province, and various respiratory or nonrespiratory comorbidities were significantly associated with mortality of NTM infection. The use of a macrolide (more than 1 year) negatively correlated with mortality of NTM infection (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI].53–.71), regardless of azithromycin (aHR 0.60, 95% CI.43–.85) or clarithromycin use (aHR 0.63, 95% CI.53–.75). Conclusions NTM-infected patients had poor prognosis when compared to TB patients or the general population, especially for NTM and TB coinfection. NTM mortality was associated with certain demographic characteristics, but long-term use of macrolides may provide survival benefits. [ABSTRACT FROM AUTHOR]

Combating disparities is a crucial goal of ongoing efforts to end the human immunodeficiency virus (HIV) epidemic. In a multivariable analysis of a cohort in the Midwestern United States, racial/ethnic disparities in HIV viral suppression were no longer robust after accounting for other sociodemographic factors. Neighborhood deprivation and low income were independently inversely associated with viral suppression. [ABSTRACT FROM AUTHOR]

Background As coronavirus disease 2019 (COVID-19) disseminates throughout the United States, a better understanding of the patient characteristics associated with hospitalization, morbidity, and mortality in diverse geographic regions is essential. Methods Hospital chargemaster data on adult patients with COVID-19 admitted to 245 hospitals across 38 states between 15 February and 20 April 2020 were assessed. The clinical course from admission, through hospitalization, and to discharge or death was analyzed. Results A total of 11 721 patients were included (majority were >60 years of age [59.9%] and male [53.4%]). Comorbidities included hypertension (46.7%), diabetes (27.8%), cardiovascular disease (18.6%), obesity (16.1%), and chronic kidney disease (12.2%). Mechanical ventilation was required by 1967 patients (16.8%). Mortality among hospitalized patients was 21.4% and increased to 70.5% among those on mechanical ventilation. Male sex, older age, obesity, geographic region, and the presence of chronic kidney disease or a preexisting cardiovascular disease were associated with increased odds of mechanical ventilation. All aforementioned risk factors, with the exception of obesity, were associated with increased odds of death (all P values <.001). Many patients received investigational medications for treatment of COVID-19, including 48 patients on remdesivir and 4232 on hydroxychloroquine. Conclusions This large observational cohort describes the clinical course and identifies factors associated with the outcomes of hospitalized patients with COVID-19 across the United States. These data can inform strategies to prioritize prevention and treatment for this disease. [ABSTRACT FROM AUTHOR]

Background As drug development has globalized, trials have increasingly enrolled participants from all parts of the world rather than just the United States and Western Europe. For antibacterial drug trials, understanding enrollment trends and regional differences is important for generalizability considerations. Methods We retrospectively analyzed 42 phase 3 trials submitted to the US Food and Drug Administration after 2001 for complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), community-acquired bacterial pneumonia (CABP), and acute bacterial skin and skin structure infection (ABSSSI) (n = 29 282 participants). Enrollment numbers, demographics, clinical characteristics, and microbiological data were compared to identify temporal and geographic trends. Results For cUTI, cIAI, and CABP trials, Eastern European enrollment greatly increased over the study period. For ABSSSI trials, North American enrollment increased. Demographic characteristics and regional microbiology among regions were broadly similar with several exceptions. For cIAI trials, Eastern European participants had the lowest proportion of participants with prior antibacterial drug therapy. For ABSSSI trials, North American participants more commonly reported intravenous drug use. Microbiological differences relative to North America included a greater proportion of Klebsiella pneumoniae among Asian cIAI isolates (17.8% vs 9.0%, P  = .0057), a higher proportion of cephalosporin resistance in South American Enterobacteriaceae cUTI isolates (26.8% vs 15.7%, P  = .044), and a lower proportion of Staphylococcus aureus in Eastern European ABSSSI isolates (43.7% vs 61.9%, P  < .0001). Conclusions Geographic trends in recruitment for recent antibacterial clinical trials differ by indication. Regional similarities in demographic characteristics and microbiology across regions lessen concerns regarding generalizability due to shifting enrollment trends. [ABSTRACT FROM AUTHOR]